Background: The impact of HIV PrEP depends on drug uptake,
adherence, sexual practices, and interactions between these factors.Methods: Participants in randomized placebo-controlled
iPrEx, ATN 089, or US PrEP Safety trials were enrolled in a 72-week open label
extension (iPrEx OLE). The study
provided services regardless of choice to receive oral FTC/TDF PrEP. Tenofovir-diphosphate (TFV-DP) was quantified
in dried blood spots (DBS) among seroconverters and a random sample of site and
visit matched seronegatives.Results: 1603 HIV-uninfected persons enrolled, of whom
76% opted to receive PrEP. Non-condom receptive anal intercourse (ncRAI) was
associated with PrEP uptake (P=0.001).
The reasons for not requesting PrEP included concern about side effects
(49%), the inconvenience of a daily pill (24%), and preference for other
prevention methods (14%). Among those starting PrEP, HIV incidence was
1.83/100PY which was 49% (95% CI: -1 to 74%) lower than among those who did not
choose PrEP after adjusting for sexual behavior, 53% (95% CI: 26 to 70%) lower
than in the placebo arm of the randomized phase (3.93/100PY), and 51% (95% CI:
23% to 69%) lower than during the gap between the randomized phase and OLE
(3.81/100PY). Incidence was lower among those with higher drug exposure.

TFV-DP in DBS (fmol/punch)

Est. dosing

% of follow-up

HIV incidence

95% CI

<2.5

None

26%

4.7/100 PY

2.8 to 7.2

2.5 to < 350

<2 tablets/wk

27%

2.2/100 PY

1.1 to 4.1

>=350 to < 700

2 to 3 tablets/wk

12%

0.6/100 PY

0.0 to 2.5

>=700 to 1249

4 to 6 tablets/wk

22%

0 /100 PY

0.0 to 0.6

>=1250

Daily

5%

0 /100 PY

0.0 to 1.1

[HIV Incidence According to TFV-DP in DBS]

Effective PrEP use (≥4 tablets/week) was
associated with older age, more schooling, ncRAI, more sexual partners, and
syphilis or herpes. The proportion
reporting ncRAI decreased from 33% to 25% among PrEP recipients (P < 0.01)
and from 27% to 20% among non-recipients (P< 0.01).Conclusions: PrEP was preferentially requested by those
reporting higher risk sexual practices; risk declined in the cohort, regardless
of PrEP receipt. The impact of oral PrEP
may be increased by these synergies and limited by non-adherence. DBS drug
concentrations are convenient and strong correlates of PrEP protection.